The present invention relates generally to the detection of volatile organic compounds that serve as biomarkers for a biological condition, such as a disease, and particularly to a noninvasive system and method for determining the presence of such condition in an individual or substance through analysis of a gaseous sample from the individual or substance.
Early detection of disease in an individual is often important to successful treatment of that disease. A variety of techniques are used to test for specific diseases either before or after symptoms occur. For example, blood samples and urine samples are routinely taken for analysis and detection of abnormalities indicative of disease. Many of these techniques are invasive or uncomfortable for the patient.
One potential noninvasive technique for determining the presence of a variety of diseases in the body of an individual is breath analysis. There are over three hundred distinct chemical compounds that may be detected in human expired breath, and each of these distinct chemical compounds has its own absorption spectrum. Studies have shown that specific alterations or changes in this expired air are indicative of specific diseases. This is true for some diseases because of the direct compositional relationship between constituents carried in the blood stream and constituents excreted into the alveolar spaces of the lungs. In any event, the changes or alterations in the constituents of an individual""s breath can be detected to determine whether the individual has a particular biological condition, such as a disease or metabolic disorder.
The presence of a given disease can be indicated by the addition or absence of one or more constituents in a gaseous sample (e.g., expired air) otherwise not present, a change in concentration of one or more constituents or a combination of the two. Thus, a successful diagnostic technique must be able to readily detect the addition or change in concentration of constituents. The addition of a constituent and/or the change in concentration of a constituent are often referred to as biochemical markers or biomarkers. Detection of biomarkers has been a complex task due to the large number of constituents within human expired air and due to the constant change of constituents that results from environmental pollutants and other components which enter an individual""s lungs.
To the present, analysis of human expired air largely has been accomplished by using gas chromatography/mass spectrometry which detects the numerous components within human-expired air. The use of a gas chromatographic/mass spectrometric technique has been necessary because of the number of constituents and because of their presence in submicrogram per liter to microgram per liter concentrations. Various statistical analyses are performed on the results with the aid of a personal computer to determine the presence of biomarkers. This technique, however, is expensive and time consuming, rendering it inappropriate for the routine testing of individuals.
The gas chromatography/mass spectrometry technique has been used in researching biomarkers associated with lung cancer. Lung cancer is a disease of particular interest due to its growing presence, severe effects and difficulty of early detection. Diagnostic techniques that have been used in the past to detect pre-symptomatic lung cancer include chest x-rays, fiber optic bronchoscopy and sputum cytology. However, these techniques are costly to administer and have not been adopted as standard screening techniques. Like the gas chromatography/mass spectrometry approach, these techniques are not amenable to large-scale use for early detection of lung cancer.
Similar problems are involved in detecting other biological conditions. For example, biomarkers contained in the gases resulting from metabolic activity in cell cultures, pathology specimens or food specimens may contain biomarkers indicative of a biological condition, such as disease, spoilage or other contamination. Photoacoustic detection has been used to determine VOCs present in certain of these types of gaseous samples, but it has been limited in its application to breath samples, due to, for example, the moisture content of breath. Water vapor tends to have high absorbance of the laser energy used in conventional photoacoustic detection across a broad spectrum.
It would be advantageous to have a quick inexpensive system and method for analyzing gaseous samples, such as the exhaled breath of an individual or the gases proximate cell cultures, pathology specimens, food specimens, etc., to determine detrimental biological conditions, such as spoilage or diseases, e.g., lung cancer, renal failure, liver disease and diabetes, for which specific biomarkers are present in human expired air.
The present invention features a system and method for detecting at least one specific volatile organic compound in a gaseous sample. The specific volatile organic compound is indicative of a biological condition when present in a given amount. The method includes obtaining a gaseous sample that has been exposed to or is suspected of being exposed to byproducts of a biological agent. A CO overtone laser is operated in a vibrational overtone sequence to generate a radiation that undergoes a characteristic intense absorption by the at least one specific volatile organic compound. The radiation is directed into the sample, and any characteristic intense absorption is detected. This provides an indication of whether the biological condition exists, based on the presence and amount of the at least one specific volatile organic compound.
According to another aspect of the invention, a system is provided for detecting a biomarker indicative of the presence of a biological condition. The system comprises a photoacoustic cell having an inlet through which a gaseous sample may be introduced into an interior of the photoacoustic cell. An overtone laser is combined with the photoacoustic cell and positioned to direct a radiation through the photoacoustic cell. The selected radiation is of a frequency predetermined for a characteristic intense absorption by at least one specific biomarker contained in the gaseous sample. The system also includes a detector coupled to the photoacoustic cell to detect the characteristic intense absorption indicative of the at least one specific biomarker.
According to another aspect of the invention, a method for detecting whether a given biomarker is present in the selected gaseous sample is disclosed. The method includes obtaining a gaseous sample and selecting a radiation in the form of an overtone laser transition occurring at a frequency such that the radiation undergoes a characteristic absorption by a given biomarker if present in the gaseous sample. The method further includes directing the radiation into the gaseous sample, and detecting whether the characteristic absorption occurs.